AU2005302506B2

AU2005302506B2 - Heterocyclical chromophore architectures

Info

Publication number: AU2005302506B2
Application number: AU2005302506A
Authority: AU
Inventors: Frederick J. Goetz Jr.; Frederick J. Goetz
Original assignee: Lightwave Logic Inc
Current assignee: Lightwave Logic Inc
Priority date: 2004-10-29
Filing date: 2005-10-26
Publication date: 2012-08-16
Anticipated expiration: 2025-10-26
Also published as: JP5241234B2; US20110178301A1; EP1805150B1; EP1805150A2; CN102304130A; JP2013067650A; JP2008519100A; WO2006050128A3; AU2005302506A1; CA2584792C; US20080139812A1; US20130345425A1; CA2584792A1; US7919619B2; CN102304130B; CN101048390A; EP1805150A4; ES2599075T3; WO2006050128A2

Abstract

NLO chromophores of the form of Formula I and the commercially acceptable salts, solvates and hydrates thereof, wherein Z,X,π,D and A have the definitions provided herein.

Description

WO 2006/050128 PCT/US2005/039010 HETEROCYCLICAL CHROMOPHORE ARCHITECTURES BACKGROUND OF THE INVENTION [0001] Polymeric electro-optic (EO) materials have demonstrated enormous potential for core application in a broad range of systems and devices, including phased array radar, satellite and fiber telecommunications, cable television (CATV), optical gyroscopes for application in aerial and missile guidance, electronic -counter measure systems (ECM) systems, backplane interconnects for high-speed computation, ultrafast analog-to-digital conversion, land mine detection, radio frequency photonics, spatial light modulation and all-optical (light-switching-light) signal processing. [0002] Nonlinear optic materials are capable of varying their first-, second-, third- and higher-order polarizabilities in the presence of an externally applied electric field or incident light (two-photon absorption). In telecommunication applications, the second-order polarizability (hyperpolarizability or 1) and third-order polarizability (second-order hyperpolarizability or y) are currently of great interest. The hyperpolarizability is related to the change of a NLO material's refractive index in response to application of an electric field. The second-order hyperpolarizability is related to the change of refractive index in response to photonic absorbance and thus is relevant to all-optical signal processing. A more complete discussion of nonlinear optical materials may be found in D. S. Chemla and J. Zyss, Nonlinear optical properties of organic molecules and crystals, Academic Press, 1987 and K.-S. Lee, Polymers for Photonics Applications I, Springer 2002. [0003] Many NLO molecules (chromophores) have been synthesized that exhibit high molecular electro-optic properties. The product of the molecular dipole moment (p) and hyperpolarizability (P) is often used as a measure of molecular electro-optic performance due to the dipole's involvement in material processing. One chromophore originally evaluated for its extraordinary NLO properties by Bell Labs in the 1960s, Disperse Red (DR), exhibits an electro optic coefficient pp ~ 580x10~ 4 8 esu. Current molecular designs, including FTC, CLD and GLD, exhibit pp values in excess of 10,000x10-4 8 esu. See Dalton et al., "New Class of High Hyperpolarizability Organic Chromophores and Process for Synthesizing the Same", WO 00/09613. [0004] Nevertheless extreme difficulties have been encountered translating microscopic molecular hyperpolarizabilities (P) into macroscopic material hyperpolarizabilities (Xf 2 )). Molecular subcomponents (chromophores) must be integrated into NLO materials that exhibit: (i) a high degree of macroscopic nonlinearity; and, (ii) sufficient temporal, thermal, chemical and WO 2006/050128 PCT/US2005/039010 photochemical stability. Simultaneous solution of these dual issues is regarded as the final impediment in the broad commercialization of EO polymers in numerous government and commercial devices and systems. [0005] The production of high material hyperpolarizabilities (X( 2 )) is limited by the poor social character of NLO chromophores. Commercially viable materials must incorporate chromophores with the requisite molecular moment statistically oriented along a single material axis. In order to achieve such an organization, the charge transfer (dipolar) character of NLO chromophores is commonly exploited through the application of an external electric field during material processing which creates a localized lower-energy condition favoring noncentrosymmetric order. Unfortunately, at even moderate chromophore densities, molecules form multi-molecular dipolarly-bound (centrosymmetric) aggregates that cannot be dismantled via realistic field energies. As a result, NLO material performance tends to decrease dramatically after approximately 20-30% weight loading. One possible solution to this situation is the production of higher performance chromophores that can produce the desired hyperpolar character at significantly lower molar concentrations. [0006] Attempts at fabricating higher performance NLO chromophores have largely failed due to the nature of the molecular architecture employed throughout the scientific community. Currently all_high-performance chromophores (e.g., CLD, FTC, GLD, etc.) incorporate protracted "naked" chains of alternating single-double -r-conjugated covalent bonds. Researchers such as Dr. Seth Marder have provided profound and detailed studies regarding the quantum mechanical function of such "bond-alternating" systems which have been invaluable to our current understanding of the origins of the NLO phenomenon and have in turn guided present-day chemical engineering efforts. Although increasing the length of these chains generally improves NLO character, once these chains exceed -2 nm, little or no improvement in material performance has been recorded. Presumably this is largely due to: (i) bending and rotation of the conjugated atomic chains which disrupts the r-conduction of the system and thus reduces the resultant NLO character; and, (ii) the inability of such large molecular systems to orient within the material matrix during poling processes due to environmental steric inhibition. Thus, future chromophore architectures must exhibit two important characteristic: (i) a high degree of rigidity, and (ii) smaller conjugative systems that concentrate NLO activity within more compact molecular dimensions. [0007] Long-term thermal, chemical and photochemical stability is the single most important issues in the construction of effective NLO materials. Material instability is in large part the result of three factors: (i) the increased susceptibility to nucleophilic attack of NLO chromophores due to 2 WO 2006/050128 PCT/US2005/039010 molecular and/or intraniolecular (CT) charge transfer or (quasi)-polarization, either due to high field poling processes or photonic absorption at molecular and intramolecular resonant energies; (ii) molecular motion due to photo-induced cis-trans isomerization which aids in the reorientation of molecules into performance-detrimental centrosymmetric configurations over time; and (iii) the extreme difficulty in incorporating NLO chromophores into a holistic cross-linked polymer matrix due to inherent reactivity of naked alternating-bond chromophore architectures. Thus, future chromophore architectures: (i) must exhibit improved CT and/or quasi-polar state stability; (ii) must not incorporate structures that undergo. photo-induced cis-trans isomerization; and (iii) must be highly resistant to polymerization processes through the possible full-exclusion of naked alternating bonds. [0008] The present invention seeks to fulfill these needs through the innovation of fully heterocyclical anti-aromatic chromophore design. The heterocyclical systems described herein do not incorporate naked bond-alternating chains that are susceptible to bending or rotation. The central anti-aromatic conductor "pull" the molecule into a quasi-CT state; since aromaticity and non-CT states are both favorably low-energy conditions, charge transfer and aromaticity within the molecular systems described herein are set against each other within a competitive theater. This competitive situation is known as CAPP engineering or Charge-Aromaticity Push Pull. As a result, the incorporation of anti-aromatic systems dramatically improves the conductive properties of the central Tr-conjugated bridge providing for smaller molecular lengths with significantly greater NLO property. Because all the systems described, herein are aromatic in their CT state and quasi-aromatic in their intermediate quasi-polarized states, this structure is expected to dramatically improve polar-state stability. Furthermore, novel electronic acceptor systems are described herein which are expected to significantly improve excited-state and quasi-CT delocalization making the overall systems less susceptible to nucleophilic attack. The heterocyclical nature of all the systems described herein forbids the existence of photo-induced cis-trans isomerization which is suspected as a cause of both material and molecular degeneration. Finally, the invention provides for chromophoric systems that are devoid of naked alternating bonds that are reactive to polymerization conditions. 3 WO 2006/050128 PCT/US2005/039010 SUMMARY OF THE INVENTION [0009] The present invention relates to NLO chromophores for the production of first-, second, third- and/or higher order polarizabilities of the form of Formula I: R(p)

Z

3 C3 X<3 R() 2 A

Z

1 C Z4 D R(p) X2 C Z 2 R(p) Formula I or an acceptable salt thereof; wherein [00010] (p) is 0-6; [00011] rvv are independently at each occurrence a covalent chemical bond; [00012] X" are independently selected from C, N, 0 or S; [00013] Z 14 are independently N, CH or CR; where R is defined below. [00014] D is an organic electron donating group having equal or lower electron affinity relative to the electron affinity of A. In the presence of Tr 1, D is attached to the remainder of the molecule at two atomic positions X 1 and X 2 . In the absence of TT 1, D is attached to the remainder of the molecule at two atomic positions Z' and C2. [00015] A is an organic electron accepting group having equal or higher electron affinity relative to the electron affinity of D. In the presence of T 2, A is attached to the remainder of the molecule at two atomic positions X3 and X4. In the absence of Tr 2, A is attached to the remainder of the molecule at two atomic positions Z 4 and C3. [00016] rr I comprises X 1 and X 2 and is absent or a bridge joining atomic pairs Z' and C2 to XlvX 2 and which provides electronic conjugation between D and an anti-aromatic system comprising C', C2, C3, C4, Z', Z 2 , Z 3 and Z 4 . [00017] n 2 comprises X 3 and X 4 and is absent or a bridge joining atomic pairs C3 and Z 4 to x 3 avX 4 and which provides electronic conjugation between A and said anti-aromatic system. 4 WO 2006/050128 PCT/US2005/039010 [00018] R is independently selected from: (i) a spacer system of the Formula II

Q

4 R4

Q--R

1 -T R3 2 U Formula Il [00019] or an acceptable salt thereof; wherein [00020] R 3 is a C 6 -CIo aryl, CG-C 10 heteroaryl, 4-10 membered heterocyclic or a C 6 -9 10 saturated cyclic group; 1 or 2 carbon atoms in the foregoing cyclic moieties are optionally substituted by an oxo (=O) moiety; and the foregoing R3 groups are optionally substituted by I to 3 R5 groups; [00021] R, and R 2 are independently selected from the list of substituents provided in the definition of R 3 , (CH 2 )t(C 6

-C

1 o aryl) or (CH 2 )t(4-10 membered heterocyclic), t is an integer ranging from 0 to 5, and the foregoing R 1 and R 2 groups are optionally substituted by I to 3 R5 groups; [00022] R 4 is independently selected from the list of substituents provided in the definition of

R

3 , a chemical bond (-), or hydrogen; [00023] each Q 1 , Q 2 , and Q 4 is independently selected from hydrogen, halo, C 1

-C

10 alkyl, C 2 C 10 alkenyl, C 2

-C

1 e alkynyl, nitro, trifluoromethyl, trifluoromethoxy, azido, -OR 5 , -NR 6 C(0)OR 5 ,

-NR

6

SO

2

R

5 , -SO 2 NR'R, -NR 6 C(O)R', -C(O)NR 5

R

6 , -NR 5

R

6 , -S(O)jR 7 wherein j is an integer ranging from 0 to 2, -NR (CR R )tOR 6 , -(CH 2 )t(C 6

-C

10 aryl), -S0 2

(CH

2 )t(C6-C 1 o aryl), -S(CH 2 )t(C 6 C 10 aryl), -O(CH 2 )t(C 6

-C

1 O aryl), -(CH 2 )t(4-10 membered heterocyclic), and -(CR R )mOR6, wherein m is an integer from 1 to 5 and t is an integer from 0 to 5; with the proviso that when R 4 is hydrogen Q 4 is not available; said alkyl group optionally contains 1 or 2 hetero moieties selected from 0, S and -N(R 6 )- said aryl and heterocyclic Q groups are optionally fused to a C6-C10 aryl group, a Cq-C 8 saturated cyclic group, or a 4-10 membered heterocyclic group; 1 or 2 carbon atoms in the foregoing heterocyclic moieties are optionally substituted by an oxo (=0) moiety; and 5 WO 2006/050128 PCT/US2005/039010 the alkyl, aryl and heterocyclic moieties of the foregoing Q groups are optionally substituted by 1 to 3 substituents independently selected from nitro, trifluoromethyl, trifluoromethoxy, azido, -NR SO 2 R', -S0 2 NR'R', -NR 6 C(O)R', -C(O)NR 5

R

6 , -NR 5 R6, -(CR 6 R )mOR wherein m 'is an integer from 1 to 5, -OR 5 and the substituents listed in the definition of R 5 ; [00024] each R 5 is independently selected from H, C-C 1 0 alkyl, -(CH 2 )t(CS-Clo aryl), and

-(CH

2 )t(4-10 membered heterocyclic), wherein t is an integer from 0 to 5; said alkyl group optionally includes I or 2 hetero moieties selected from 0, S and -N(R )- said aryl and heterocyclic R 5 groups are optionally fused to a C6-C 1 o aryl group, a C 5 -Ce saturated cyclic group, or a 4-10 membered heterocyclic group; and the foregoing R9 subsituents, except H, are optionally substituted by 1 to 3 substituents independently selected from nitro, trifluoromethyl, trifluoromethoxy, azido, -NR 6

C(O)R

7 , -C(O)NR 6

R

7 , -NR 6

R

7 , hydroxy, C-C 6 alkyl, and. C1-C6 alkoxy; [00025] each R and R is independently H or C-C 6 alkyl; [00G26] T, U and V are each independently selected from C (carbon), 0 (oxygen), N (nitrogen), and S (sulfur), and are included within R ; [00027] T, U, and V are immediately adjacent to one another; and [00028] W is any non-hydrogen atom in R 3 that is not T, U, or V; or [00029] (ii) hydrogen, halo, C-C 1 o alkyl, C 2

-C

10 alkenyl, C 2

-C

10 alkynyl, nitro, trifluoromethyl, trifluoromethoxy, azido, -OR 5 , -NR 5

C(O)OR

5 , -NR'SO 2 R', -SO 2 NR'R -NR6C(O)R 5 , -C(O)NR 5

R

6 , -NR 5 R', -S(O)jR 7 wherein j is an integer ranging from 0 to 2,

-NR

5 (CRsR 7 )tOR 6 , -(CH 2 )t(C6-C 1 o aryl), -S0 2

(CH

2 )t(Co-C 1 0 aryl), -S(CH 2 )t(Cs-C 1 o aryl), -O(CH 2 )t(C 6 C1 0 aryl), -(CH 2 )t(4-10 membered heterocyclic), and -(CR 6

R

7 )mOR6, wherein m is an integer from 1 to 5 and t is an integer from 0 to 5; said alkyl group optionally contains 1 or 2 hetero moieties selected from 0, S and -N(R 6 )- , wherein R5, R6 and R7 are as defined above. [00030] Another embodiment of the present invention refers to the compounds of Formula I wherein the Tr conjugative bridge and C 2 and Z' of the anti-aromatic system are connected in a manner selected from the group consisting of: X I C2 x2 C2 cx X I Z 1 =N,cHorCR XjZ X2CHorCR

Z

1 N. CH or cR z x6,x 2 =c 6 WO 2006/050128 PCT/US2005/039010 C2 X2 Z 1

Z

1 ' N, CH. r CR xn X1,

X

2 = C 0<n<4 C2 X2 Cl X1 1Z 1 Z= N, CH or CR Xc2 X X2 C X Z Z= N, CH or CR N C2 n I, X2 = C X N n Z1, X1, X2 =C 0<n<4 N CZ C2 R N X2 Z 1 N, CH or CR C Z=N,CHorCR X1 N n Xi, X2 = C X lNCo 0 <n <4 XJ"Z1 Ci X1, X2 = C [00031] Wherein R is as defined above. [00032] Another embodiment of the present invention refers to the compounds of Formula I wherein the electron donating group (D) and X 1 and X 2 of the Tr' conjugative bridge are connected in a manner selected from the group consisting of: RR 2 N N R N X1 2 Xi, 2 = X1, X2 =C X - XZ, L I 1X X1, X2 C Z=N,CHorCR 7 WO 2006/050128 PCT/US2005/039010 R [ XX

X,X

2 =C - Z=N,CHorCR R R N NN N N ,X2 I X1 X 2 =C Z XX2=C Z=N,CHorCR ZN,CHorCR zx X2 X1 1X X x~x= X1, X2= C - X1, X2= C 2= [00033] And wherein R is as defined above. [000341 Another embodiment of the present invention refers to the compounds of Formula I wherein the TT2 conjugative bridge and C 3 and Z 4 of the anti-aromatic system are connected in a manner selected from the group consisting of: X3 C X3 C313 4 C1 4 Z 4 = N, CH orCR X4 14 4 Z 4 N, CH orCR NZ4 X, X4 =C Z47 C X3,X 4 =C L C 14 Z 4 =N,CHorCR - Z4 X 3 , X 4 C 8 WO 2006/050128 PCT/US2005/039010 3C3 C3 X4 Z 4 ,= N, CH or CR . X3 Z 4

Z

4 =N,CHorCR X3, X4 C n X 3 , X4 = C O<n<4 3 R X3 C- -- C4 X3 N C

X

4 Z Z 4 =NCH orCR Z 4 = N,CHorCR n X 3

,X

4 =CX4 C4 X 3 , X 4 = C o<n<4 Z N C 3 N C

X

3 N Z4 Z4 =N, CH or CR X 4 N Z4 Z 4 =N,CH orCR 4n n X 3 , X 4 = C 0<n<4 0<n<4 [00035] Wherein R is as defined above. [00036] Another embodiment of the present invention refers to the compounds of Formula I wherein the electron accepting group (A) and X 3 and X 4 of the Tr2 conjugative bridge are connected in a manner selected from the group consisting of; Acc Acc 4 Acc Acc Ac Acex N Ac AX c Acc Acc R R N Acc N Acc Xx4N N Acc x4 AxC X N N Acc Acc 9 WO 2006/050128 PCT/US2005/039010 [00037] wherein R is defined above independently at each occurrence; and, Acc is an electron accepting group selected from CN, NO 2 , SO 2 R and 0 < n < 5. [00038] Another nonlimiting example of the invention includes the following chromophore: R N No 2 N N02 RN N NO2 R R0 wherein R is defined above, independently at each occurrence. [00039] Another nonlimiting example of the invention includes the following chromophore: R I4 N4 No2 N N N NO 2 RN N N R R wherein R is defined above, independently at each occurrence. [00040] In this invention the term "nonlinear optic chromophore" (NLOC) is defined as molecules or portions of a molecule that create a nonlinear optic effect when irradiated with light. The chromophores are any molecular unit whose interaction with light gives rise to the nonlinear optical effect. The desired effect may occur at resonant or nonresonant wavelengths. The activity of a specific chromophore in a nonlinear optic material is stated as their hyper-polarizability, which is directly related to the molecular dipole moment of the chromophore. [00041] In this invention, the term "halo," unless otherwise indicated, includes fluoro, chloro, bromo or iodo. Preferred halo groups are fluoro, chloro and bromo. 10 WO 2006/050128 PCT/US2005/039010 [00042] The term "afkyl," as.used herein, unless otherwise indicated, includes saturated monovalent hydrocarbon radicals having straight, cyclic or branched moieties. It is understood that for cyclic moieties at least three carbon atoms are required in said alkyl group. [00043] The term 'alkenyl," as used herein, unless otherwise indicated, includes monovalent hydrocarbon radicals having at least one carbon-carbon double bond and also having straight, cyclic or branched moieties 's provided above in the definition of "alkyl." [00044] The term "alkynyl,'' as used herein, unless otherwise indicated, includes monovalent hydrocarbon radicals having at least one carbon-carbon triple bond and also having straight, cyclic or branched moieties as provided above in the definition ,of alkyll." [00045] The term "alkoxy," as used herein, unless otherwise indicated, includes 0-alkyl groups wherein "alkyl" is as defined above. [00046] The term "aryl," as used herein, unless otherwise indicated, includes an organic radical derived from an aromatic hydrocarbon by removal of one hydrogen, such as phenyl or naphthyl. [00047] The term "heteroaryl," as used herein, unless otherwise indicated, includes an organic radical derived by removal of one hydrogen atom from a carbon atom in the ring of a heteroaromatic hydrocarbon, containing one or more heteroatoms independently selected from 0, S, and N. Heteroaryl groups must have at least 5 atoms in their ring system and are optionally substituted independently with 0-2 halogen, trifluoromethyl, C-C 6 alkoxy, Cl-r alkyl, or nitro groups. [00048] The term "4-10 membered heterocyclic,' as used herein, unless otherwise indicated, includes aromatic and non-aromatic heterocyclic groups containing one or more heteroatoms each selected from OS and N, wherein each heterocyclic group has from 4-10 atoms in its ring system. Non-aromatic heterocyclic groups include groups having only 4 atoms in their ring system, but aromatic heterocyclic groups must have at least 5 atoms in their ring system. An example of a 4 membered heterocyclic group is azetidinyl (derived from azetidine). An example of a 5 membered heterocyclic group is thiazoly) and an example of a 10 membered heterocyclic group is quinolinyl. Examples of non-aromatic heterocyclic groups are pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, tetrahydropyrany, tetrahydrothiopyranyl, piperidino, morpholino, thiomorpholino, thioxanyl, piperazinyl, azetidinyl, oxetanyl, thietanyl, homopiperidinyl, oxepanyl, thiepanyl, oxazepinyl, diazepinyl, thiazepinyl, 1,2,3,6-tetrahydropyridinyl, 2-pyrrolinyl, 3 pyrrolinyl, indolinyl, 2H-pyranyl, 4H-pyranyl, dioxanyl, 1,3-dioxolanyl, pyrazolinyl, dithianyl, dithiolanyl, dihydropyranyl, dihydrothienyl, dihydrofuranyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, 3-azabicyclo[3.1.0]hexanyl, 3-azabicyclo[4.1.0]heptanyl, 3 H-indolyl and quinolizinyl. Examples of aromatic heterocyclic groups are pyridinyl, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, cinnolinyl, indazolyl, indolizinyl, phthalazinyl, 11 WO 2006/050128 PCT/US2005/039010 pyridazinyl, triazinyl, isoindolyl, pteridinyl, purinyl, oxadiazolyl, thiadiazolyl, furazanyl, benzofurazanyl, benzothiophenyl, benzothiazolyl, benzoxazolyl, quinazolinyl, quinoxalinyl, naphthyridinyl, and furopyridinyl. The foregoing groups, as derived from the compounds listed above, may be C-attached or N-attached where such is possible. For instance, a group derived from pyrrole may be pyrrol-1-yl (N-attached) or pyrrol-3-yl (C-attached). [00049] The term "saturated cyclic group" as used herein, unless otherwise indicated, includes non-aromatic, fully saturated cyclic moieties wherein alkyl is as defined above. [00050] The phrase "acceptable salt(s)", as used herein, unless otherwise indicated, includes salts of acidic or basic groups which may be present in the compounds of the invention. The compounds of the invention that are basic in nature are capable of forming a wide variety of salts with various inorganic and organic acids. The acids that may be used to prepare pharmaceutically acceptable acid addition salts of such basic compounds of the invention are those that form non-toxic acid addition salts, i.e., salts containing pharmacologically acceptable anions, such as the hydrochloride, hydrobramide, hydroiodide, nitrate, sulfate, bisulfate, phosphate, acid phosphate, isonicotinate acetate, lactate, salicylate, citrate, acid citrate, tartrate, pantothenate, bitartrate, ascorbate, succinate, maleate, gentisinate, fumarate, gluconate, glucaronate, saccharate, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate and pamoate [i.e., 1,1'-methylene-bis-(2-hydroxy-3 naphthoate)] salts. [00051] Those compounds of the invention that are acidic in nature are capable of forming base salts with various pharmacologically acceptable cations. Examples of such salts include the alkali metal or alkaline earth metal salts and particularly the sodium and potassium salts. [00052] The term "solvate," as used herein includes a compound of the invention or a salt thereof, that further includes a stoichiometric or non-stoichiometric amount of a solvent bound by non-covalent intermolecular forces. [00053] The term "hydrate," as used herein refers to a compound of the invention or a salt thereof, that further includes a stoichiometric or non-stoichiometric amount of water bound by non-covalent intermolecular forces. [00054] Certain compounds of the present invention may have asymmetric centers and therefore appear in different enantiomeric forms. This invention relates to the use of all optical isomers and stereoisomers of the compounds of the invention and mixtures thereof. The compounds of the invention may also appear as tautomers. This invention relates to the use of all such tautomers and mixtures thereof. [00055] The subject invention also includes isotopically-labelled compounds, and the commercially acceptable salts thereof, which are identical to those recited in Formulas I and 1l but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of 12 WO 2006/050128 PCT/US2005/039010 isotopes that can be incorporated into compounds of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, sulfur, fluorine and chlorine, such as 2 H, 3 H, ' 3 C, 14 C, 1 5 N, 18017, O S, "'F, and 31CI, respectively. Compounds of the present invention and commercially acceptable salts of said compounds which contain the aforementioned isotopes and/or other isotopes of other atoms are within the scope of this invention. Certain isotopically-labelledcompounds of the present invention, for example those into which radioactive isotopes such as 3H and 14C are incorporated, are'useful in drug and/or substrate tissue distribution assays. Tritiated, i.e. 'H, and carbon-14, i.e., 1C, isotopes are particularly preferred for their ease of preparation and detectability. Further, substitution with heavier isotopes such as deuterium, i.e., 2 H, can afford certain advantages resulting from greater stability. Isotopically labelled compounds of Formula I of this invention can generally be prepared by carrying out the procedures disclosed in the Schemes and/or in the Examples and Preparations below, by substituting a readily available isotopically labelled reagent for a non-isotopically labelled reagent. [00066] Each of the patents, patent applications, published International applications, and scientific publications referred to in this patent application is incorporated herein by reference in its entirety. DETAILED DESCRIPTION OF THE INVENTION [00057] The compounds of Formula I are useful structures for the production of NLO effects. [00058] The first-order hyperpolarizability (P) is one of the most common and useful NLO properties. Higher-order hyperpolarizabilities are useful in other applications such as all-optical (light-switching-light) applications. To determine if a material, such as a compound or polymer, includes a nonlinear optic chromophore with first-order hyperpolar character, the following test may be performed. First, the material in the form of a thin film is placed in an electric field to align the dipoles. This may be performed by sandwiching a film of the material between electrodes, such as indium tin oxide (ITO) substrates, gold films, or silver films, for example. [00059] To generate a poling electric field, an electric potential is then applied to the electrodes while the material is heated to near its glass transition (Tg) temperature. After a suitable period of time, the temperature is gradually lowered while maintaining the poling electric field. Alternatively, the material can be poled by corona poling method, where an electrically charged needle at a suitable distance from the material film provides the poling electric field, In either instance, the dipoles in the material tend to align with the field. [00060] The nonlinear optical property of the poled material is then tested as follows. Polarized light, often from a laser, is passed through the poled material, then through a polarizing filter, and to a light intensity detector. If the intensity of light received at the detector changes as the electric potential applied to the electrodes is varied, the material incorporates a nonlinear optic chromophore and has an electro-optically variable refractive index. A more detailed 13 WO 2006/050128 PCT/US2005/039010 discussion of techniques to measure the electro-optic constants of a poled film that incorporates nonlinear optic chromophores may be found in Chia-Chi Teng, Measuring Electro-Optic Constants of a Poled Film, in Nonlinear Optics of Organic Molecules and Polymers, Chp. 7, 447 49 (Hari Singh Nalwa & Seizo Miyata eds., 1997), incorporated by reference in its entirety, except that in the event of any inconsistent disclosure or definition from the present application, the disclosure or definition herein shall be deemed to prevail. [00061] The relationship between the change in applied electric potential versus the change in the refractive index of the material may be represented as its EO coefficient r so. This effect is commonly referred to as an electro-optic, or EO, effect. Devices that include materials that change their refractive index in response to changes in an applied electric potential are called electro-optical (EO) devices, 14 WO 2006/050128 PCT/US2005/039010 [00062] An example compound of the Formula I may be prepared according to the following reaction scheme. R, in the reaction scheme and discussion that follow, is as defined above. OH

R-NH

2 , 12 120"C R HO R NH 1) 0 3 S H

N

2

NH

2 2) Na 2

S

2 04 HNE NaOH IHN R H R I No NN

NO

2 +0 N (, & NO 2 2 (H 3

C)

2 N No 1) A with Base N __________ H -H 2 0 -HX 2) Reduce with

NO

2

-

2 Sn(OAc) 2 HN R R.N N02 N N H3C 0 NO 2 N N

CH

3 R 15 WO 2006/050128 PCT/US2005/039010 [00063] Another example compound of the Formula I may be prepared according to the following reaction scheme. R, in the reaction scheme and discussion that follow, is as defined above. NH2 NHa. H 2 0 CuO

(NH

4

)

2

SO

3 Trichlorobenzene 165*C under 150'C, -H 2 0 pressure

H

3 cO H 3 CO OH

OCH

3 N N 0R-NH- 2 , 12 1) BBr 3 in CH2Ci 2 "1200 2) NaHCO 3 R R HO

H

3 C0 I NH H O N N 1) 03 N NH 2 2) Na 2

S

2 04 NaOH FNN N H HN H R *R + II N N 2 + NO O~ N O 2 N O+ ( I2 N

(HAP)

2 1) A with Base N 1 N -H,0 2) Reduce with H -HX Sn(OAC) 2 NOR -H 2 N NO2 HN NO 1N 1N N N N 16NO 2

H

3 N N CHs 16 16a AnnlITIONAL EXAMPLES: Actual Syntheses Carried Out: NLU onromopnortot;i uliluld 1, vitetiii euuli R represerits (1) a mesity moiety, (ii) the elected 2-ethylhexyl moiety, and (iii) a sulfone species: 5 Ca 3 H3CO 10 ' O C1 3

SO

2 15 were each separately prepared in accordance with the general reaction scheme set forth in paragraph 100062], above, and their syntheses are described in detail in the following paragraphs. 20 (1) Synthesis of an NLO Chromophore of Formula / wherein R is mesitvi: Step I: Synthesis of 2,6-bis(mesitylamino)naphthalene via Bucherer Rxn OH MsNH 25 +2 MsNH 2 OH MsN H Chemical Fornula: CIH 8 02 Chemical Formula: C2 8

H

30

N

2 Exact Mass: 160.05 Exact Mass: 394,2409 Molecular Weight: 160.17 Molecular Weight: 394.24 30 In a 3-necked vessel (1.5 L capacity) equipped with argon and a Dean-Stark trap is added a mixture of 405 g (3.0 M) of mesitylamine (MW 135.2; 2, 4, 6- trimethylaniline) and 45 g of iodine crystals (0.36 M). The mixture is stirred by hand and heated to 120CC. At this point 160g of dihydroxynaphthalene is added. The vessel is closed and heated with mechanical stirring to 190*C. Heating is continued overnight and the hot mixture is 35 poured into a beaker. The crude material is recrystallized once from methanol, and then a second recrystallization from chloroform provides the pure material as a yellow powder. Electrospray mass spectroscopy gave a parent ion at 394.4 amu. NMR (Proton in DM0S): d 7.25 (d, 2H), 7.05 (s, 2H), 6.94 (s, 4H), 6.84 (d of d, 2H), 6.21 (d, 2H), 2.26 (s, 6H), 2.10 (s, 12H). 40 45 16b Step II: Azo-coupling (SP represents mesityl) 39 Ep 5 A- A h| N H9 SPAReagent A NMP/pyr, 5'C-RT FW = 394.55 HCwou=p FW=577.23

C

2 8 1 30

N

2

C

3 4

H

4

N.;O

3 ~ 15 To a three-neck 1L beaker, with argon purge and magnetic stirring, is added 200mL NMP, 20mL pyridine and 20g (51 mmol) of Ms-Diamine (fw = 394 g/mol), from Step 1. The solution is cooled in a water ice-bath until the temperature is below 5"C. Then 9.34g (51 mmol or 1eq) of SPA-Reagent (fw = 184.17 g/mol) is added. The solution will turn purple almost immediately. The solution is allowed to reach room temperature. This 20 process of adding SPA (cooling to 5*C, addition of an additional equivalent of SPA, and then warming to room temperature) is repeated until the TLC indicates there is no starting material remaining, i.e., an addition of approximately 3 equivalents of SPA reagent. The equivalents were added every two hours. TLC shows a mixture of product and di-substituted byproduct (minus nitrogen) and other regio-isomers. TLC and HPLC 25 Conditions: TLC - 80/20 Methanol/Water, C18 RP; HPLC; 90110 Methanol/Water on C18 RP Waters Delta-Pak Column (part #WAT0I 1797) Step Ill: Ring-annulation 30 <K PW= 150 CH, 35 I2 Ho 4p FW 578.72 C34HwN403 FW= 709.88 Exact Mass =

C

4 2H 4

IN

6 ONS 578.24 Exact Mass 40 709.30 To a 1OOmL flask with magnetic stirring, under argon, is added 65mL of acetic acid, 7mL of pyridine and 7g (12.1 mmol) of material from Step 2 (fw = 577.23) at 40*C. To this is added 1.82g (1 eq or 12.1 mmol) N,N-dimethyl-4-nitrosoaniline (fw = 150). A few hours 45 later, an additional .91g (0.5 eq or 6.1 mmol) N,N-dimethyl-4-nitrosoaniline is added. The reaction is run overnight at 40 0 C. The reaction can be monitored by 90/10 Methanol/Waters RP TLC. The reaction is considered complete when the starting material is no longer present. The reason for the additional % equivalent added a few hours later is that the TLC showed remaining starting material. The product can be seen 50 with 60/40 MeCl 2 /MeOH RP TLC.

16c Step IV(a): Reduction 5 N' N Sn Y, AcoH, 10 HN W =57872 FW540.72

C

34 Ha 4

N

4 03 3 5 H5 Exact Mass= 578.24 Exact Mass ' 540.31 15 To a 10OmL reaction flask with magnetic stirring, under argon, is added 5OmL acetic acid and 5mL NMP. To this is added 5g (7.1 mmol) of material from Step 3 (FW = 708.29). The solution is allowed to dissolve for 30 minutes. 4 equivalents (1.5g in this preparation) 20 of metallic tin powder (Aldrich 100 mesh, 99.5%) is weighed out. Every 15 minutes or so, a small amount of tin (tip of spatula) is added. The reaction is closely monitored with 80/20 MeOH/MeCl 2 RP TLC until the starting material is gone and the product spot appears close to the plate origin. 5g of material takes about 4 hours to reduce. The reaction color will proceed from green, to greenish-brown, to brown, to brownish-red, to 25 red. The TLC tends to happen all at once, the first hour or so will show nothing at all, then will rapidly proceed to the starting material. After the TLC shows only product, the tin must be filtered off as soon as possible to halt the reaction. Step IV(b): Ring Closure 30 N5H C, Cs"0Etn SW -540.72 FW =703.79 40 BVMa s= Exact Mss- 703.29 540.51 To a 125mL beaker with magnetic stirring, under argon, is added 3.37g (22 mmol) of CsF (FW = 152). To this is added 1.53g (6.2 mmol) of Picryl Chloride and 70mL of anhydrous 45 Ethanol. The oil bath is heated to 55*C while the Picryl Chloride and CsF react. The solution turns orange. Then 3.00g (5.6 mmol) of material from Step 4a (FW = 540) is added to begin the reaction. The reaction will take three to four days to run and is tracked by electrospray mass spec. 50 The compound thus prepared was evaluated for NLO characteristics in accordance with the evaluation procedure set forth in paragraphs [00057]-[00061], above. The compound exhibited NLO characteristics.

16d (ii) Synthesis of an NLO Chromophore of Formula I where R is the elected 2-ethylhexyl: Step I 5 OH NH 10 HO ColH 8 02 HN Mol. Wt,: 160,17 1I 15 Mol. Wt.: 382.63 In a 3-necked flask (1.5 L capacity) equipped with argon and a Dean-Stark trap is added a mixture of 388 g (3.0 M) of 2-ethyl-hexylamine (MW 129.15) and 45 g of iodine crystals (0.36M). The mixture is stirred by hand and heated to 1200C. At this point 160 g of 20 dihydroxynaphthalene is added. The vessel is closed and heated with mechanical stirring to 1900C. Heating is continued overnight and the hot mixture is poured into a beaker. The crude material is ground in methanol and the precipitated product is collected. Step II: 25 NH 30 H HN H HNH 35 HN MC.Wt.32.63

C

32 1?1 46

N

1 0 3 S Ml W 32.63 t 566.8 SO 40 To a three-neck 1L flask, with argon purge and magnetic stirring, is added 380mL N-methylpyrrolidine (NMP), 38 mL pyridine and 38g (.1 mol) of diamine (fw = 383 g/mol). The solution is allowed to dissolve and deaerate. The solution is then cooled in a water ice-bath until the temperature is below 5*C. Then 18.32g (.1 mol or 1 eq) of SPA 45 Reagent (fw = 184.17 g/mol) is added. The solution will turn purple almost immediately. The solution is allowed to reach room temperature. This process of adding SPA (cooling to 5 0 C, addition of an additional equivalent of SPA, and then warming to room temperature) is repeated until the TLC indicates there is no starting material remaining. 50 16e Step Ill: 5 NH NH NN N NH 2 NH 10 Mo!. Wt.: 69S.96 Mol. Wt.; 529.R To a beaker with magnetic stirring, under argon, is added 550mL of acetic acid, 50mL of 15 pyridine and 57g (0.1 mol) of the product of Step 2 (fw = 566.8) at 40'C. To this is added 15.Og (1 eq or 0.1 mol) N,N-dimethyl-4-nitrosoaniline (fw = 150). A few hours later, an additional 7.5g (0.5 eq or 0.5 mol) N,N-dimethyl-4-nitrosoaniline is added. The reaction is run overnight at 40"C. The reaction is considered complete when the starting material is no longer present by TLC. The product is precipitated out with water and collected on a 20 Buchner funnel with vacuum. The precipitant is washed with boiling water until the filtrate is colorless. Step IV(a): Reduction 25 NH H NH 30 N NNH2 N N SO 35

C

40

H

5 4N 6 0 3 3 cH51Ns Mcl, Wt: 698.96 Mot Wt.: 529.8 To a reaction flask with magnetic stirring, under argon, is added 700mL acetic acid and 40 70mL NMP. The flask is purged with argon for 15 minutes. To this is added 70g (0.1 mol) of the product of Step 3 (FW = 698.96). The solution is allowed to dissolve for 30 minutes. Every 15 minutes or so, a small amount of metallic tin (tip of spatula) is added. The reaction is closely monitored via TLC until the starting material is gone and the product spot appears. 45 The reaction is vacuum filtered on a Buchner funnel to filter off excess metallic tin and tin salts. The product is precipitated out in water, basified with NaOH and collected. The product is thoroughly dried. 50 1 6f Step IV(b): Ring Closure 5 V1 NH 10 NH2 Mo Wt: 529.8

M

0 4 9 N86 Mcd. t.: 29.8Mol. Wt.: 691.86 15 To a flask with magnetic stirring, under argon, is added 60.8g (0.4 mol) of CsF (FW = 152). The glass, its joints and the CsF are thoroughly dried with a heat gun to remove as much moisture as possible. To this is added 27.2g (0.11 mmol) of Picryl Chloride (FW = 247) and 600mL of anhydrous ethanol. 53g (0.1 mol) of the product of Step 4 (FW = 540) 20 is added to begin the reaction. The reaction will take three to four days to run and is tracked by electron spray mass spec. The compound thus prepared, evaluated for NLO characteristics in accordance with the evaluation procedure set forth in paragraphs [00057]-[00061], above, exhibits 25 NLO characteristics. (iii) Synthesis of an NLO Chromophore of Formula I wherein R is a sulfone: Synthesis of the Elected Sulfone Spacer Species - Steps 1-6: Step 1: Production of 2,5-dibutoxy-3,4,6-trimethylbenzene 30 35 01-i 0 CHQ 02Hr Exact Mass: 26421

C

9 11-I 1202 C 4

H

5 Br Mol. Wt.: 264.40 ExactMass: [52.08 Exact Masst 135.99 Ml. Wi. 152.19 Mol WE: 137.02 40 In a 5 L vessel with mechanical stirring over a heating mantel, 2 L of acetone is heated to 50 0 C under argon with 500 g (3.3 mol) of trimethylhydroquinone and 900 g (6.6 mol) of 1 bromobutane. To this solution, under rapid stirring, 600 ml of 50% sodium hydroxide 45 solution is slowly added by hand over approximately two hours. The reaction is monitored via HPLC the next day using a reverse phase column and 90 % Methanol/ 10 % Distilled Water or TLC'd on reverse phase plates with 90 % Methanol/ 10% Water. Using HPLC the product will come out at about 5 minutes with an absorbance at 282.9. The reaction mixture can be diluted with methanol and injected directly. Using TLC, the diol will go to 50 the top of the plate; the mono-reacted will travel faster than the product, the di-reacted. A shortwave UV light is necessary to view the plate. Once complete the reaction is filtered to remove the sodium bromide that will precipitate out of solution. The salt cake is washed with MeCl 2 to ensure that all product is collected. The filtrate is then added to a 4 L separatory funnel or two 2 L funnels and the filtering flask is washed with MeCl 2 as 16g well. The product layer will separate out and is then washed succt;E-.sr.ivnly with dib itro (10 %) Rnrliiim hyr1rnviri qrnlidiinn.und thQn lAith iuntnr tn rnmnvn thn hinOW. Tho produot, in the form of a nrmb-r liquid, nedJ5 to bc Jd iii a rulcuy vvapuatuI tilylitly lilyhlc ui around the boiling point of 1-bromobutane (100-104 C). 5 Step 2: Synthesis of 1-chloromethyl-2,5-di butoxy-3,4,6-trimethyl benzene 10 Exco Mass: 26421 Eaci:Mass: 312 9 M01. Wt,: 264.40 mos. Wt: 31267 C1 In a 2 L flask with mechanical stirring, 264 g (1.0 mol) of starting material is combined 15 with 250ml of acetic acid, 500 ml of hydrochloric acid and 250 mi of phosphoric acid. The vessel is heated via a heating mantel to 85-90*C under argon. Then at temperature, 100 grams of paraformaldehyde is slowly added to the reaction over a period of two to three hours. The second day the reaction should be monitored via HPLC or TLC and an additional 50 to 100 grams of paraformaldehyde may be added to assure completion of 20 the reaction. HPLC is done with a reverse phase C18 column using a flow rate of 2 ml/min and 100 % methanol or 90% methanol and 10 % DMF; the product will appear at -5.7 minutes with an absorbance at 286.4. If using TLC a solution of 90 % methanol and 10 % water on a reverse phase plate is used. The benzyl chloride will travel slower on the plate. A short wave length light is necessary to see the spots on the plate. Once 25 complete, the reaction is allowed to reach room temperature, after which the product precipitates out typically in hard pellets. The product is extracted with a Buchner funnel and washed with copious quantities of water. The product is dried in a desiccating cabinet until it can be easily crushed with a mortar and pestle. Precautions, including a face-mask, should be used during this procedure. The solution is then allowed to stir in 1 30 2 L of 70 % methanol/ 30% water and filtered again through a Buchner funnel. The cake is washed with cold 50/50 methanol and water and allowed to dry. The pure product is a slightly yellow powder. Step 3 Synthesis of 1 -methaneth iol-2,5-bisbutoxy-3,4,6-trimethy benzene 35 . 40 .XNX2X' .- ..... X .QC,1,,OS Mol. WI.: 12. 7 Mn. W.:l2 Mol. W.: 353.54 H2N NH 2 0 45 1Ma Wc: 310.49 In a 3 L flask with mechanical stirring under argon, 114 g (1.5 mol) of thiourea (FW = 50 76.1) is added to 500 ml of water. The mixture is heated to reflux temperature until dissolved. Subsequently 312 g of starting material (1.0 mol) is added to the reaction with 500 ml of ethanol. The reaction is heated for at least two hours (under reflux). The first step of the reaction, creation of the benzylisothiouronium derivative, occurs in approximately 30 minutes. This is indicated by a miscible solution. The full two hour time -l Uh period assures aiiipleeiess of the reaction. 120 g (1 5 mol) of 50% sodium hydroxide solution is dissolved in 200 ml of water and added to the reaction in a slow stream by hand. The solution is heated for an hour under reflux in order to create the desired methanethiol derivative. The reaction is tracked via HPLC or TLC. HPLC is done with a 5 reverse phase C18 column using a flow rate of 2 ml/min and 90 % methanol and 10 % water; the product will appear at early between 2 to 3 minutes before the benzyl chloride with an absorbance at 286.2. If using TLC a solution of 100% methanol or 90 % methanol and 10 % DMF on a reverse phase plate is used and the benzyl chloride is run on the plate as well. A short wave lamp is necessary to see the spots. The heat source is turned 10 off and the solution is allowed to cool overnight under vigorous stirring. Rapid stirring assures the precipitation of the product as a yellow powder. The product is filtered with a Buchner funnel, washed with a large quantity of water and allowed to dry. The dried thiol is tested via HPLC and if some impurities are noted by some small early peaks the product can be powered and extracted with 50/50 methanol and water. The product is 15 only slightly soluble in methanol. The product is then filtered again and allowed to dry. Step 4: Synthesis of 1-(benzyl(3-chloropropyl)sulfide)-2,5-bisbutoxy-3,4,6 trimethylbenze 20 25 Md. Wt.! 3.Ml, w.. 337.02 C1 Exact Mass: 15S.93 Mat. Wt.: 157.14 C 30 310 g (1.0 mol) of the benzyl thiol from the prior step is added to a 3 L flask along with 156 g (1.0 mol) of 1-bromo-3-chloropropane and approximately 1000 ml of methanol, under argon with rapid stirring. The thiol will not dissolve; however, it will go into solution as the reaction proceeds during the sodium hydroxide addition. The reaction requires no heat. 80 g of 50% sodium hydroxide solution is weighed out and washed into an addition 35 funnel with approximately 200 ml of water. The sodium hydroxide solution is slowly dripped into the reaction over approximately one to two hours. The reaction is allowed to stir for another hour to assure completion of the reaction. The reaction can be monitored via HPLC, TLC or Mass Spec. HPLC is done with a reverse phase C18 column using a flow rate of 2 mlmin and 90 % methanol and 10 % water; the product will appear at 6-7 40 minutes as a broad peak absorbing at 204.0 and 280.5. If using TLC a solution of 100 % methanol or 90% methanol and 10 % DMF on a reverse phase plate is often used; however, 10% DMF instead of water and 100% methanol may give better separation. A short wave lamp is necessary to view the results. The reaction is added to a separatory funnel, washing out the vessel with -500 ml of dichloromethane. 45 Approximately 500 ml of water is added to the separatory funnel and the product layer is washed twice with water and the organic layer rotovaped at high temperature to remove excess 1-bromo-3-chloropropane (bp -140"C). The product sulfide is a yellow, orange or brown viscous liquid/oil. 50 16i Step 5: Synthesis of 1-(benzyl(3-chloropropyl)sulfone)-2,5-bisbutoxy-3,4,6 tri methyl benzene 5 D

LC'

1

H

5 5 CI04S Exact Mass: 418.19 Mal. Wt: 419.U2 10 C11is e~ 1 0Bxacat Ma's: 386.20 Mol. Wt.: 387.02 ClI 15 386 gm (1.0 mol) of the chlorosulfide from the prior step is added to 2 L of acetic acid in a 5 L flask equipped with a mechanical stirrer, thermometer, and heating mantel and heated to 30*C. Approximately 400 gm (2.5 mol) of potassium permanganate (FW = 158) (solubility in water 640 g/L) is weighed out and put in a jar. Then approximately 25 grams of the 400 is stirred into 250 ml of water and a small portion of the mixture is poured into 20 the reaction. The reaction will exotherm of its own accord. This is repeated over a 4 to 6 hour interval until all of the 400 grams of the potassium permanganate is used up. Weighing out the 400 gm first permits one to track how much KMnO 4 is used. The solution will turn purple and then brown; if the solution remains purple wait until the solution turns brown before adding more KMnO 4 . The following day, the reaction mixture 25 is analyzed via HPLC to monitor its progress. A reverse phase C18 column with a flow rate of 2ml/min and 90% MeOH/10% water is used. The product will appear at 3.6 min with an absorbance at 205.2 and 284.1. TLC can be used as well using 100% MeOH or 90% methanol and 10% DMF on reverse phase plates. A short wave lamp is necessary to view the results. Typically, the reaction is not complete and an addition 100 to 200 gm 30 of granular potassium permanganate is added to the reaction in teaspoon increments over an extended period of time typically 4 to 6 hours. This procedure is repeated each day until the reaction is complete (typically about three days). Once complete the heat source is removed and sulfur dioxide gas is bubble through the reaction to reduce the remaining permanganate, until the solution becomes very light yellow. The reaction is 35 then divided into two 4 L beakers and cooled with copious amounts of ice if the reaction is still above the boiling temperature of dichloromethane. Once cool, approximately 500 ml of dichloromethane is added to each beaker and stirred (by hand or magnetically) and then allowed to settle (preferably over several hours or overnight) until a light yellow product-layer appears at the bottom of the beakers. The top layer may than be decanted 40 and the bottom dichloromethane layer washed with water, allowed again to separate, and washed successively. The two beakers may than be combined in a 2 or 4 L separatory funnel. Allowed again to settle, preferably washed again, and added to a rotary evaporation flask and rotovaped to remove any excess water (bp - 1000C). The product sulfone is a yellow, orange or brown viscous liquidloil which will solidify over several 45 hours at room temperature. Step 6: Synthesis of 1-(benzyl(3-iodopropyl)sulfone)-2,5-bisbutoxy-3,4,6 trimethylbenzene 50 00

CI

16j 418 gm (1.0 mol) of tho culfono from tho prior atop is dissolved in approximately I L Ur aceluitj und htEiled to ~55*C with under argon. 600 gm (4.0 mol) of sodium iodine (1-W = 150) is added. The reaction is run for two to three days. (Additional sodium iodine may be 5 added to increase the reaction rate). The reaction is monitored by HPLC or TLC. HPLC is executed on a reverse phase C18 column, in 90% methanol 10% water with a flow rate of 2 mi/min, the chlorinated product has a retention time of approximately 3.6 minutes. The iodinated product comes out slightly later at 4.7 minutes. The chloride has a low peak absorbance at 205.2 and a slightly higher absorbance at 284.1. TLC is done using 10 reverse phase plates and a solution of 100% methanol or 90% methanol and 10% DMF the iodo travels slower than the chloro and two spots are apparent with a short wave lamp. Once the reaction is determined to be complete, the product is extracted with copious amounts of water and dichloromethane and washed twice with water in a separatory funnel. The product is rotovaped to dryness. 15 Synthesis of a Chromophore With Sulfone Spacer - Steps 7a-1 1c: Step 7a: Synthesis of2,6-diaminonaphthalene via Bucherer Reaction OH NI-b 20 +2 NH 3 25 HO H2N Chemical Fonula: C 0 HgO2 Chemical Fonula- CiofioN 2 ExactMass: 160.05 ExactlVass: 158.08 MolecularWeight: 160.17 Molecular Weight 158.20 30 In a Parr 4848 pressure reactor vessel (1.5 L capacity) is added 160.2 gm (1 M) of 2,6 dihydroxynaphthalene. Then to the vessel is added a solution of 420 gm (3.12F) of ammonium sulfite monohydrate, (NH4)2SO 3 * H 2 0, in 400 ml of water and 380 ml of 28% ammonia solution (5.6 M of NH 3 ) in water. The mixture is stirred by hand and the 35 pressure reactor is closed and heated with mechanical stirring to 1500C. The contents of the pressure reactor are removed and suspended in 1 L of argon outgassed water. The suspension is filtered and washed with 2 L of argon outgassed water and then with a cold solution of 80% methanol and 20% water. The diamino-naphthalene is dried in a desiccating cabinet over anhydrous calcium sulfate. The product tested for purity via 40 HPLC using a C18 reverse phase column and 90% methanol/10% water and via Mass Spec. The product will appear early close to 3 minutes and shows the finger low absorbance pattern of amines and higher absorbance bands at 277.0, 323.2, and 361.7. This procedure follows the preparation of 2-Naphthylamine as documented by Nathan L. Drake in Organic Reactions, Vol 1, page 120. 45 Step 7b: Synthesis of 2,6-Bis[N-(HBM-propyl-benzyl sulfone) amino]-naphthalene; 5: H2N NH OnmicaFonula: Ohilt6 S ClemicalFammu : Cicfl32 Clfmical FoTmula: CZHN 2 OS2 ar Me: 510.13 R'crtm: 158.03 EMotMss: 92252 ovlrsr&t:S51.

4 7 lvblculrWMilt 15820 lecnhsr Weigh: 921-31 16k To a 1 L round bottom flask under argon purge at room temperature is added 500 ml of DMF and 7.9 gm (0.05 M) of 2,6-diaminonaphthalene. The mixture is stirred until dissolved. Then 10.6 gm of very finely powered potassium phosphate tribasic (0.05 FW) 5 is added to the reaction. The reaction is stirred for 5 minutes; then, 25.5 gm of the jodo spacer group (product of spacer synthesis, step 6) is added in 3 to 4 portions over 2 hours. The following day 10.6 grams of very finely powered potassium phosphate tribasic (0.05 FV) is added to the reaction. The reaction is stirred for 5 minutes; then, 25.5 gm of the spacing group is added in 3 to 4 portions over 2 hours. The reaction is monitored via 10 HPLC. The reaction may take several weeks at room temperature. The reaction mixture upon completion is added to 1 liter of water and filtered. Then the cake is washed with water and methanol. The cake is first dried, then powered and boiled in ethanol, refiltered, and dried again in order to purify the product. 15 Step 8: Rxn of {2,6-Bis[N-(HBM-propyl-benzyl sulfone) amino]-naphthalene} w/ SPA Reagent 20 - / NH 25 n,-ogm ~sa 2 N 30 MylcolarWeilft 1107.49 In a 500 ml round bottom flask under argon with a mechanical stirrer and a low 35 temperature thermometer that is set in a water bath for ice is added 350 ml of NMP. Then 36.9 gm (.03 M) of the product of step 7b is added and stirred until dissolved. Ice and some acetone are added to the water bath until the temperature reaches 0CC. The 1 ml of pyridine is added to the reaction followed by 1.12 gm of SPA Reagent. This is repeated over 4-5 hours until 5 ml (0.03 F) of pyridine and 5.6 gm (0.03 F) of SPA 40 Reagent have been added to the reaction. The reaction must be maintained at a temperature between 0-5cC. If the reaction supports an intense purple color then a longer interval should be maintained between additions of the pyridine and SPA Reagent. The color of the reaction will turn from intense purple to brown-red. Once all the pyridine and SPA Reagent have been added the reaction is allow to stir overnight in the ice bath. 45 In the morning, the reaction is tested using TLC on reverse phase plates using 80% methanol/20% water. The mono-substituted product will travel % of the way up the plate; the di-substituted will travel closer to the top of the plate. The di-substituted product should be avoided as it is useless for the next step. The substituted products are visible without the aid of a short wave lamp. The starting material is visible using a short wave 50 lamp. The reaction is also tracked using HPLC using a C18 reverse phase column and 90% methanoll10% water. The mono and di are not clearly separated; however, the starting naphthyl diamine is. If the reaction is not complete, that is, if naphthyl diamine is present and no di-substituted product is apparent then an additional 1 ml of pyridine and 1.12 gm of SPA Reagent may be added after the temperature is stabilized within the 0- 161 5*C range. After each addition and a wait time of at least one hour the reaction is TLC'd again. This can be repeated until the first appearance of di-substituted is present, at which point the reaction is stopped. The reaction mixture is rinsed into a 1 liter beaker equipped with a stir bar with water (100 to 200 ml). As the reaction mixture is stirred 500 5 ml of concentrated HCI is added to the reaction and the mixture is allowed to stir for at least one hour. The precipitated product is filtered and washed with water until the filtrate is clear and not acidic via pH paper. The product is dried in a desiccating cabinet. Step 9: Rxn with N,N-dimethyl-4-nitrosoanaline and cyclization to 3-N-(HBM 10 propyl-benzylsulfone)amino-(4-zwitterionic protenated SPA)-7-(HBM-propyl-benzyl sulfone )-9-aminobenzofa]phenazine 15NN N ~ 6P02 NO \/ SOS 20 N N \S Mulecular Weighu 1107.49 \-NH N NN 25 EMNlMW.,123767 C, 64.05; 1r,7.17: N. 3.7:0.14.22:5,7.77 To a 1 L flask with a heating source is added 440 ml of acetic acid and 44 ml of pyridine 30 and the solution is mechanically stirred and degassed with argon for 1/2 hour. Then 44.3 gm (0.04M) of the product of step 8 is added and argon is bubbled through the solution as the material dissolves in the acetic for at least another 1/2 hour. The solution is not heated, and after a few minutes 6.0 gm of N,N-dimethyl-4-nitrosoanaline is added to the reaction over several hours. After 1 hour after the last addition the reaction is tested via 35 TLC on reverse phase plates in two solution 90% methanol/10% water and 80% methanol/20% MeC1 2 . The first solution will indicate if azo starting material or bis-azo (which will not react) still remains in the solution; the second solution will show the product as a green spot. The reaction may be left to stir overnight at room temperature and up to 2 equivalents of additional nitroso compound may be added. The 40 disappearance of the azo indicated that the reaction is complete. Then an excess of cold water is added to the reaction and the reaction filtered. The precipitate needs to be washed with water until no more N,N-dimethyl-4-nitrosoanaline is in the reaction mixture. This is indicated by a yellow color in the filtrate; however, TLC in methanol/methylene chloride will indicate a yellow spot near the top of the plate if nitroso still is present in the 45 reaction mixture. The precipitate is then analyzed by TLC and Mass Spec. Step 10: Reduction of 3-N-(HBM-propyl-benzyl sulfone)amino-(4-zwitterionic protenated SPA)-7-(HBM-propyl-benzyl sulfone)-9-amino-benzo[a]phenazine to the amine analogue through the removal of the SPA blocking group 50 In a 500 ml flask without heat but equipped with a magnetic stirrer is added 310 ml of acetic acid. The acetic acid is de-aerated with argon for at least one half (112) hour. Then 31 gm of the zwitterionic starting material from the prior step (- 0.025M) is added to the acetic acid. Then over a 6 hour period 16 gm of metallic tin power (100 mesh, 99.5%) is 16m added %A gram at a time. The reaction is monitored by HPLC using a C18 reverse phase column and 70% methanol, 20% acetonitrile, 5% ethyl acetate, and 5% distilled water andlor by TLC using reverse phase plate and 80% methanol and 20% methylene chloride. Once the reaction is complete (indicated by the absence of the starting 5 material), the excess tin is filtered off and washed with a small amount of acetic acid. After the filtrate is washed into a beaker a moderate amount of ice is added to the filtrate and put on a magnetic stirrer. Then 300 ml of concentrated HCl is slowly added with vigorous stirring. The product will precipitate out of the solution. If the mixture appears sticky additional ice and water can be added with stirring. The product is filtered and 10 washed with water (washed with cold methanol/water or cold methanol to dry). The product is analyzed for purity via Mass Spec, HPLC, and TLC. Step 11a: Synthesis of Pyridinium Picrate (Pyridine Picrate) from Picric Acid for the preparation of Picryl Chloride 15 OH oH H 0 2 N

NO

2 o 2 N

NO

2 N 20

NO

2

NO

2 C1,N30 CIIHSN 4 07 EaoilRUS: 22D2CC C 1 1 1

N

4 07 Exact Mass: 308.04 Ma;.WI.: 229W1 FRd Mass: 205.04 Mai. wt.: 308.20 ik290 234 7W, M01. Wt: 300.20 MA.'; 25 231.0( 71/.), 229.99 ([.1%) dnJ .: 0 ,0.4 04.7 ,28;N OO ,63 c, 3il5;F t.L32; N. 1 E.34:O0,A4.8F C, 42.87; H, 2.02; 1.90 334 c428;H 26;N,1.L;O3.4 To a 3L three neck flask in a heating mantel with mechanical stirring and a thermometer is added 2L of ethanol. While stirring, the temperature is raised to 75*C and maintained 30 at that temperature. While stirring, 229 gm (1.OM) of dry picric acid is added. After the picric acid is dissolved, 90 ml (1.11 M) of pyridine is very slowly added with an addition funnel. Following the addition of pyridine the flask is removed from the oil bath and the mechanical stirrer is also removed. The flask and its contents are allowed to cool to room temperature. The flask and its contents are allowed to cool overnight in the freezer 35 compartment of a refrigerator. The next day the contents of the flask are filtered and the contents of the flask washed into the funnel with a trace amount of ethanol. No further washing is necessary. The final product is air dried in a fume hood. The theoretical yield is 308 gm of which a 95-98% yield can be expected. Pyridinium picrate (pyridine picrate) has a m.p. of 166*C. Other analysis is not usually done on this intermediate. 40 Step 11 b: Synthesis of Picryl Chloride from Pyridinium Picrate 45 0 2 N NO, C1 + + POCI 3 )I- 0 2 N NO 2 50 NO 2 C11 IHN4N(f 7

NO

2 Exat Mass: 308.04 NO ML W 302 Exact Mass: 246.96 C,42.87;,2.62;N, 18,18;,36,34 C 9 l. L Wt .: 247 55 C, 4.87;11, .62;N, 1, 19 0, 6.34C, 29.1 1; H, 0.8 1; C1, 14.32;N, 16.97; 0, 38.78 10n To a 3L three neck flask in a heating mantel with mechanical stirring and a thermometer is added 600ml of dry benzene. While stirring, the temperature is raised to 50"C and maintained at that temperature. Then 462 gm (1.5F) of pyridinium picrate (pyridine picrate from step 9a) is carefully added. The temperature is then raised to 75*C. After the 5 pryidinium picrate is dissolved, carefully and very slowly 103 ml (11M) of phosphory chloride is dripped into the reaction via an addition funnel. The temperature is then elevated to reflux temperature (80-85*C) and the suspension is refluxed for 15-30 minutes. The heat source is then removed and the reaction is allowed to stir and cool to 50-60*C. Then with continuous mechanical stirring, 1L of water preheated to 60 0 C is 10 slowly and carefully added. The reaction mixture is separated in a separatory funnel. The upper layer is saved into a beaker stirred with 100 gm of sodium sulfate and filtered through a cake of anhydrous magnesium sulfate. The cake is then washed with 100ml of dry benzene. The resulting filtrate is then cooled to room temperature to deposit the first crop of Picryl Chloride (m.p. 79-80*C). The first crop is filtered and the filtrate saved for 15 additional crops, the picryl chloride is normally not washed. Additional crops may be collected by concentrating the saved filtrate on a rotovap and allowing the solution to cool. The theoretical yield is 371 gm; however, a 73% yield is reported as a first crop by Boyer, Spencer and Wright (See Note). NOTE: The above procedure is a minor modification of the procedure of Boyer, Spencer and Wright, Can J. Research 24B, 202 20 (1946). Step 11c: Synthesis of the final chromophore: 25 N 30N N-'0 N S 30 U Th1 ww S02 0 C H 20a42+

NO

2 Mal. Wt. 1069.48 0 2 N C5 5

H

85

N

7

O

12

S

2 35 Mal. Wt.: 232.55 To a flask with magnetic stirring, under argon, is added 6.08g (0.04 mol) of CsF (FW = 152). The glass, its joints and the CsF are thoroughly dried with a heat gun to remove as much moisture as possible. To this is added 2.71g (0.011 mol) of Picryl Chloride (FW = 247) and 180mL of anhydrous Ethanol. 10.7g (0.01 mol) of the product of Step 10 (FW = 40 1069.48) is added. The reaction will take three to four days to run and is tracked by electro spray mass spec and HPLC. The compound thus prepared was evaluated for NLO characteristics in accordance with the evaluation procedure set out in paragraphs [00057]- [00061] above. 45 The compound exhibited NLO characteristics. Comparison to General Synthetic Scheme Set Forth in Paragraph (00062 Each of the above three syntheses was carried out in accordance with the general reaction scheme set forth at Paragraph [00062] above. The only deviation from 50 the scheme set forth therein and those described above is the reversal of the order of the last two steps. Comprises/comprising and grammatical variations thereof when used in this specification are to be taken to specify the presence of stated features, integers, steps or 16o componanta or group thereof, but do not preclude the presence or addition of onic or more other features, integers, steps, components or groups thereof.

Claims

1. NLO chromophores of the form of Formula 1: R(p) Z 3 CX R(p) 2 .2 XA X 1 C Z4 X D E R(p) R(p) Formula I or an acceptable salt thereof; wherein (p) is 0-6; /vv are independently at each occurrence a covalent chemical bond; X1~4 are independently selected from C, N, 0 or S; Z** are independently N, CH or CR; D is an organic electron donating group having equal or lower electron affinity relative to the electron affinity of A wherein in the presence of Tr , D is attached to the two atomic positions X' and X 2 and in the absence of T, D is attached to the two atomic positions Z' and C2; A is an organic electron accepting group having equal or higher electron affinity relative to the electron affinity of D wherein in the presence of Tr 2, A is attached to the two atomic positions X3 and X 4 and in the absence of T 2, A is attached to the two atomic positions Z 4 and C3; Tr 1 comprises X 1 and X 2 and is absent or a bridge joining atomic pairs Z, and C2 to XlfVX 2 and provides electronic conjugation between D and an anti-aromatic system comprising C', C2, C3, C4, ZI, Z 2 , Z3 and Z 4 ; Tr 2 comprises X 3 and X 4 and is absent or a bridge joining atomic pairs C3 and Z 4 to X 3 ivX 4 and provides electronic conjugation between A and said anti-aromatic system; R is independently selected from: (i) a spacer system of the Formula 11 17 WO 2006/050128 PCT/US2005/039010 Q 4 R4 Q 1 -R 1 -T R 3 R2-Q2 U Formula 11 or a commercially acceptable salt thereof; wherein R 3 is a C-C1o aryl, Cs-CIo heteroaryl, 4-10 membered heterocyclic or a C 6 -C 10 saturated cyclic group; 1 or 2 carbon atoms in the foregoing cyclic moieties are optionally substituted by an oxo (=0) moiety; and the foregoing R 3 groups are optionally substituted by I to 3 R 5 groups; R 1 and R 2 are independently selected from the list of substituents provided in the definition of R 3 , (CH 2 )t(C 6 -C 1 O aryl) or (CH 2 )t(4-10 membered heterocyclic), t is an integer ranging from 0 to 5, and the foregoing R 1 and R 2 groups are optionally substituted by I to 3 R6 groups; R 4 is independently selected from the list of substituents provided in the definition of R 3 , a chemical bond ( - ), or hydrogen; each Q', Q 2 , and Q 4 is independently selected from hydrogen, halo, C1-C10 alkyl, C2-Cla alkenyl, C2-CI alkynyl, nitro, trifluoromethyl, trifluoromethoxy, azido, -OR5, -NR 6 C(0)OR 5 , -NR 6 SO 2 R 5 , -SO 2 NR'R', -NR 6 C(O)R', -C(O)NRR 6 , -NR 5 R 6 , -S(O);R 7 wherein j is an integer ranging from 0 to 2, -NR 5 (CR 6 R 7 )tOR 6 , -(CH 2 )t(Cs-C 1 e aryl), -S0 2 (CH 2 )(CG-C 10 aryl), -S(CH 2 )t(C 6 67 6 C10 aryl), -O(CH 2 )t(C 6 -C 1 0 aryl), -(CH 2 )t(4-10 membered heterocyclic), and -(CR6R )mOR , wherein m is an integer from I to 5 and t is an integer from 0 to 5; with the proviso that when R 4 is hydrogen Q 4 is not available; said alkyl group optionally contains I or 2 hetero moieties selected from 0, S and -N(R )- said aryl and heterocyclic Q groups are optionally fused to a C 6 -C1o aryl group, a C5-Ca saturated cyclic group, or a 4-10 membered heterocyclic group; 1 or 2 carbon atoms in the foregoing heterocyclic moieties are optionally substituted by an oxo (=0) moiety; and the alkyl, aryl and heterocyclic moieties of the foregoing Q groups are optionally substituted by 1 to 3 substituents independently selected from nitro, trifluoromethyl, trifluoromethoxy, azido, -NR'S0 2 R", -SO 2 NR5R 6 , -NR 6 C(O)R 5 , ~-C(O)NR R6, -NR R', -(CR 6 R 7 )mOR 6 wherein m is an integer from 1 to 5, -OR 5 and the substituents listed in the definition of R 5 ; 18 WO 2006/050128 PCT/US2005/039010 each R& is independently selected from H, C 1 -C 1 0 alkyl, -(CH 2 )t(C 6 -C 1 0 aryl), and -(CH 2 )t(4-10 membered heterocyclic), wherein t is an integer from 0 to 5; said alkyl group optionally includes 1 or 2 hetero moieties selected from 0, S, and -N(R 6 )- said aryl and heterocyclic R6 groups are optionally fused to a Cs-Cloaryl group, a C 5 -C 8 saturated cyclic group, or a 4-10 membered heterocyclic group; and the foregoing R 5 subsituents, except H, are optionally substituted by I to 3 substituents independently selected from nitro, trifluoromethyl, trifluoromethoxy, 'azido, -NR 6 C(O)R 7 , -C(O)NRR', -NR 6 R 7 , hydroxy, C 1 -C 6 alkyl, and C-C alkoxy; each R6 and R7 is independently H or C 1 -C 6 alkyl; T, U and V are each'independently selected from C (carbon), 0 (oxygen), N (nitrogen), and S (sulfur), and are included within R 3 ; T, U, and V are immediately adjacent to one another; and W is any non-hydrogen atom in R 3 that is not T, U, or V; or (ii) hydrogen, halo, C-C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, nitro. trifluorornethyi, trifluoromethoxy, azido, -OR 5 , -NR 6 C(O)OR 5 , -NR 6 SO 2 R 5 , -SO 2 NR5R 6 , -NR 6 C(O)R', C(O)NRsR 6 , -NR 5 R 6 , -S(O)jR 7 wherein j is an integer ranging from 0 to 2, -NR'(CRR)tOR', -(CH 2 )t(Ca-C 10 aryl), -S0 2 (CH 2 )t(C 6 -C 10 aryl), -S(CH 2 )t(C 6 -C 10 aryl), -O(CH 2 )i(C 6 -C 1 o aryl), -(CH 2 )t(4-10 membered heterocyclic), and -(CR 6 R 7 )mOR 6 , wherein m is an integer from I to 5 and t is an integer from 0 to 5; said alkyl group optionally contains I or 2 hetero moieties selected from 0, S and -N(R 6 )- , wherein R 5 , R 6 and R 7 are as defined above.

2. An NLO chromophore according to claim 1, wherein the Tr' conjugative bridge and C 2 and Z' of the anti-aromatic system are connected in a manner selected from the group consisting of: x 2 C2 X2 C CcX ZX N,CHorCR XZ1 = N, CH or CR C1 ZI=N,CHor1CR ZX X1, X2 = C C2 X1 Z =N, CHor CR 0<n<4 19 20 X2 F1 = i CHIrCR X' Z ZNCHorCR n X\X2.C 0<n<4 X2. N1 X2 5 £Wn' CK1j,Xt.X2*c - - 0<nC4 R C1 2 N Z=N,CHorCR X1 N CHorCR O<n<4 wherein R s as defined in claim 1

3. An NLO chromophore according to claim I or 2, wherein electron donating group (D) 10 and X 1 anc X 2 of the T-r conjugative bridge are connected in a manner selected from the group consisting of: RR 202 R X XX CX1. X1, X2 , R R Z - N, CH or CR 15 NN X2 R 2 I X CC3 -- .2 = N, CH orCR - R - 2X1,X2 , 20 25 21 NN NN xXX2, 5X x C [ , N Z=NCHor0R Z -NCH orCR 10 x and wherein R is as defined in claim 1. 15 4. An NLD chromophore according to any one of claims 1 to 3 wherein the -rr 2 conjugative bridge and C3 and Z 4 of the anti-aromatic system are connected in a manner selected frcm the group consisting of: 20 X3 'N 20 L -N, CHorOR 14 Z4 N, CH or OR x 4 Z N C z4 X3 X4 WC 24 X3, X4' C X4 z=NCFiorCR z 4 X3, X 4 C 25 Z4=N. CHorCR L NX3 N Z Z 4 N. CH orCR O<nC4 30 x1 I || 4N,C orCR XN Z N, H r R3 d Z 4 = N, CH of CR n.4 Z C 4 X 3 , X 4 C G~n<4L 22 N C C C X3N Z4 =N, CHorGR X4 24 = Z N,CH arCR 5OX3.

4 fl X 3 ,XO C .- -~ 4 + * O<n<4 wherein R is as defined in claim 1 and the r 2 conjugative bridge is attached at atomic positions X 3 -X 4 to the electron-accepting system (A).

5. An NLO chromophore according to any one of claims 1 to 4 wherein the electron 10 accepting group (A) and X 3 and X 4 of the T 2 conjugative bridge are connected in a manner selected from the group consisting of: Acc Acc Acc 1 5NXAc c A cc Acc Acc Acc R R Acc Acc N N Ace 201Q10 NA N N N Acc Ace and wherein R is as defined in claim 1, Acc is an electron accepting group selected from ON, NO 2 , SO 2 Rand 0 <n <5. WO 2006/050128 PCT/US2005/039010

6. An NLO chromophore according to claim I wherein said, chromophore is represented by the structure: R N NN2 NN N N N2 R R wherein R is as defined in claim 1.

7. An NLO chromophore according to claim I wherein said chromophore is represented by the structure: R N02 NN N O 2 N N N-N NO 2 N 0N R R wherein R is as defined in claim 1. 23